The Role of the Transcription Factor Nrf2 As a Potential Enhancer of Hepatic Regeneration

Introduction: The liver has a remarkable capacity for regeneration following hepatectomy; however, acute hepatic failure remains a significant and often fatal complication following major hepatectomy. The transcription factor Nrf2 plays a pivotal role as a master regulator of cyto-protection against oxidative stress, nevertheless, its role in hepatic regeneration is still ill-defined. We sought to investigate the prospect of Nrf2 as a potential enhancer of hepatic regeneration, which could pave the way for promising translational outcomes. Methods: A mouse model was used utilising C57BL/6 J mice and 2/3 partial hepatectomy was performed, followed by culling the mice at different time points. Pharmacological induction of Nrf2 was implemented by intra-peritoneal administration of CDDO-Me pre and post op. Nrf2 knockout mice were used as negative controls. Western blots for the proliferation marker PCNA were performed, and correlated to Nrf2 and Nrf2 downstream protein NQO1. Gene expression of the Nrf2 dependent proteins was investigated using qPCR. Results: A significant correlation between the increase of proliferation and Nrf2 activity was observed at 48 hours post-hepatectomy especially in the CDDO-Me treated mice as compared to the non-treated and knockout mice. The Nrf2 knockout mice showed decrease in proliferation at 24 hours post-hepatectomy as compared to the other 2 groups. Conclusion: The transcription factor Nrf2 has a potential major role at the early stages of liver regeneration. Pharmacological or dietary induction of Nrf2 pre and post major hepatectomy could be a simple and effective way of decreasing the incidence of the devastating occurrence of post-hepatectomy liver failure.